This project studies the immunology of schizophrenia and encompasses three lines of investigation: studies of possible autoimmune and infectious etiologies of schizophrenia, of cerebral spinal fluid for antibodies, lymphocytes, or cytotoxin factors, and of the in vivo effects of antipsychotic agents on immune function. One major task of current research is the investigation of genotypic and phenotypic markers of peripheral lymphocytes. In particular, we are studying the HLA haplotypes of patients with schizophrenia and simultaneously evaluating markers of T and B lymphocyte subpopulations in selected patients using flow cytometry. Preliminary evidence indicates that approximately 30% of schizophrenic patients tested have an elevated number of CD5- positive B lymphocytes present in their peripheral blood. This finding is intriguing because approximately 30% of patients with rheumatoid arthritis and Sjogrens syndrome have similar elevations in these cells that spontaneously produce autoantibodies. We are concurrently evaluating CSF samples for antibodies, lymphocytes, or cytotoxic or cytotrophic factors in an attempt to investigate possible central nervous system evidence of immune or infectious contributions to the pathology of schizophrenia. These nascent studies involve autoradiography, immunohistochemistry, and in vitro measures of cell growth, and are being done in collaboration with Dr. Candice Pert and Peptide Designs. The third line of investigation involves the use of flow cytometry and mitogen stimulation to evaluate the acute in vivo effects of typical and atypical antipsychotic agents on immune function. Lymphocytes from patients on the 4-East research ward are studied on a regular basis in order to test whether fluphenazine, thioridazine or clozapine modify the phenotype expression on function of lymphocytes from schizophrenic patients under drug free and medicated conditions.